Lymphocytes in the mouse (as well as other species) are divided into two major functionally-distinct classes, T cells (thymus-derived) and B cells (bone marrow-derived). Our studies focus on: 1) differentiation of B cells in ontogeny and their relative sensitivity; 2) the defect in B cell maturation in the CBA/N mouse which appears to define a relatively immature B cell subclass; 3) the activation requirements for normal B cells, particularly their sensitivity to thymus-independent antigens, anti-immunoglobulin and anti-idiotype reagents; and 4) the influence of T cells at various stages of differentiation upon the responses of B cells.